This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is associated with a NIDA K01award to obtain training in the imaging genetics of smoking in adults with and without Attention Deficit Hyperactivity Disorder (ADHD). More specifically, the research plan investigates the underlying mechanisms of smoking in 100 young adults by examining the associations between smoking, prefrontal-limbic brain circuitry, dopamine genes, and ADHD. For this purpose, four groups of young adults will be recruited: (1) 25 smokers with ADHD;(2) 25 nonsmokers with ADHD;(3) 25 normative control smokers;and (4) 25 normative control nonsmokers. Smoking will be assessed via questionnaires and salivary cotinine levels. Prefrontal-limbic brain circuitry will be examined via funtional Magnetic Resonance Imaging (fMRI), Diffusion Tensor Imaging (DTI), and Near-Infrared Spectroscopy (NIRS). Candidate genes will be the dopamine receptor (DRD4) and transporter (DAT1). Each nonsmoker will undergo a DTI scan and an fMRI scan during an experimental task consisting of mathematical problems and unpleasant and neutral pictures. Smokers will undergo a DTI scan, one NIRS session, and two fMRI scans during similar experimental tasks under the following two conditions: (1) after smoking a cigarette and (2) after overnight abstinence. The findings will provide information on the effects of smoking and abstinence on prefrontal-limbic brain circuitry in smokers with and without ADHD. In addition, the study will explore smoking in individuals with DRD4 and DAT1 and their potential interaction with prefrontal-limbic brain circuitry.